The observation that neuroendocrine peptide hormones are produced by lymphocytes and that cells of the immune system have specific receptors for neuroendocrine hormones now provides a molecualr basis for the interactions between the nervous, endocrine, and immune systems. Our results detecting the production of immunoreactive growth hormone (irGH) from lymphocytes is yet another instance in which the immune system is shown to produce a hormone commonly found in the neuroendocrine system. Growth hormone is of particular interest since it is the hormonal link between somatic development and its regulation by the central nervous system. The ultimate goal of this project is to determine the biological significance of lymphocyte-derived GH. The early focus in these studies will be to determine the structure of GH by comparing the differences or similarities of GH mRNA in lymphocytes versus pituitary cells. We will also determine the structure and biological activity of lymphocyte-derived GH and compare the similarities to pituitary GH. We plan to study the factors that stimulate or inhibit the production of lymphocyte-derived GH and determine the phenotype(s) of the GH producer cells. One of the primary factors which will be studied is growth hormone releasing hormone (GHRH) and its lymphocyte receptor. Finally, we are proposing to study the immunoregulatory role of lymphocyte- derived GH in vitro and its endocrinologic action in vivo. We expect the results of these studies will increase our understanding of immunophysiology and establish the role of GH in the commonality between the neuroendocrine and immune systems.